Refillable drug delivery by affinity homing
Inventors
Assignees
Publication Number
US-11806407-B2
Publication Date
2023-11-07
Expiration Date
2039-04-05
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Abstract
Described herein are compositions and methods for a novel drug delivery platform using affinity homing. Also disclosed herein are a drug delivery system, methods for using the novel drug delivery platform and a kit.
Core Innovation
The invention provides a novel drug delivery platform based on affinity homing, comprising a thermoresponsive hydrogel that contains a cucurbit[n]uril moiety (where n is an integer from 5-8) and a polymer. This hydrogel has a gelation temperature between 25°C and 35°C and can serve as a localized drug depot, being injectable and forming in situ at physiologic temperatures. A key feature is the hydrogel's ability to reversibly bind therapeutic agents that are coupled to guest ligands with high affinity for the cucurbit[n]uril moiety.
The problem addressed by the invention is the lack of effective and selective ways to deliver small molecule therapeutics to their intended site of action within the body, which often leads to poor regional selectivity, increased toxicity, and the need for higher systemic doses. Existing targeting approaches, such as antibody-drug conjugates, have shown extremely limited localization at disease sites despite high in vitro affinities. This invention seeks improved strategies for targeting and localizing drugs to enhance small molecule drug practice.
The drug delivery system allows therapeutic agents to be dosed systemically yet accumulate at the hydrogel site due to supramolecular affinity for the cucurbit[n]uril host presented in the hydrogel. The guest ligand attached to the therapeutic agent is selected for high binding affinity (often >10^10 M−1) and is linked to the drug by a labile linker that permits controlled drug release at the target site through hydrolysis, enzymatic action, or metabolic processes. This platform supports modular and refillable therapy, temporal tuning of drug availability, and combination therapies using the same localized depot.
Claims Coverage
The patent includes one independent claim outlining a drug delivery system with multiple inventive features.
Drug delivery system comprising a thermoresponsive hydrogel with cucurbit[n]uril moiety and PEO-PPO block copolymer
The system consists of a thermoresponsive hydrogel comprising: - A cucurbit[n]uril moiety, wherein n is an integer from 5–8. - A first polymer, which is a thermoresponsive polymer consisting of a block copolymer of polyethylene oxide (PEO) and polypropylene oxide (PPO). - The hydrogel has a gelation temperature between 25°C and 35°C. - At least one therapeutic agent is reversibly bound to the thermoresponsive hydrogel.
In summary, the patent provides coverage for a drug delivery system that uses a cucurbit[n]uril-containing, thermoresponsive PEO-PPO hydrogel capable of reversible and controlled binding of therapeutic agents.
Stated Advantages
Improves regional selectivity of drug delivery, reducing toxic off-target activity and allowing lower required doses.
Enables systemic refilling of localized drug depots, allowing remote modulation of drug function at biomedical devices or implants.
Permits temporal tuning of therapeutic activity and modular switching of drugs for combination therapy.
Increases the maximum tolerated dose by attenuating off-site toxicity of small molecule drugs via prodrugs.
Reduces risk of overdose, as drugs are only released locally after linker cleavage.
Provides biocompatible hydrogels with high water content and desirable mechanical properties such as injectability and self-healing.
Documented Applications
Treatment of cancer, including delivery of anti-cancer drugs such as doxorubicin to solid tumors via peri-tumoral depot.
Pain management following surgical incision using prolonged release of sodium channel blocking anesthetics and analgesic or anti-inflammatory drugs at the surgical site.
Localized anti-inflammatory therapy for implanted biomedical devices, for reducing inflammation and modulating immune responses at device interfaces.
Prolonged release of analgesics, anti-infective, cardiovascular, tissue regenerating, anti-diabetic drugs, vaccine antigens, peptides, proteins, ocular drugs, or nanoparticle formulations.
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